Guidelines for the Prevention and Treatment of Opportunistic Infections in HIV-Infected Adults and Adolescents

The information in the brief version is excerpted directly from the full-text guidelines. The brief version is a compilation of the tables and boxed recommendations.

Pneumocystis Pneumonia

Last Updated: July 25, 2017; Last Reviewed: July 25, 2017

Recommendations for Prevention and Treatment of Pneumocystis Pneumonia (PCP)
Preventing 1st Episode of PCP (Primary Prophylaxis)

Indications for Initiating Primary Prophylaxis:
  • CD4 count <200 cells/mm3 (AI) or
  • CD4% <14% of total lymphocyte count (BII) or
  • CD4 count >200 but <250 cells/mm3, if ART cannot be initiated, and if CD4 cell count monitoring (e.g., every 3 months) is not possible (BII).
Note—Patients who are receiving pyrimethamine/sulfadiazine for treatment or suppression of toxoplasmosis do not require additional prophylaxis for PCP (AII).

Preferred Therapy:
  • TMP-SMX, 1 DS PO dailya (AI) or
  • TMP-SMX, 1 SS PO dailya (AI).
Alternative Therapy:
  • TMP-SMX 1 DS PO three times weekly (BI) or
  • Dapsoneb,c 100 mg PO daily or 50 mg PO BID (BI) or
  • Dapsoneb 50 mg PO daily + (pyrimethamine 50 mg + leucovorin 25 mg) PO weekly (BI) or
  • (Dapsoneb 200 mg + pyrimethamine 75 mg + leucovorin 25 mg) PO weekly (BI) or
  • Aerosolized pentamidinec 300 mg via Respigard II™ nebulizer every month (BI) or
  • Atovaquone 1500 mg PO daily with food (BI) or
  • (Atovaquone 1500 mg + pyrimethamine 25 mg + leucovorin 10 mg) PO daily with food (CIII).
Indication for Discontinuing Primary Prophylaxis:
  • CD4 count increased from <200 cells/mm3 to ≥200 cells/mm3 for at least 3 months in response to ART (AI)
  • Can consider if CD4 count 100-200 cells/mm3 and HIV RNA remain below limit of detection for at least 3-6 months (BII)
Indication for Restarting Primary Prophylaxis:
  • CD4 count <100 cells/mm3 regardless of HIV RNA (AIII)
  • CD4 count 100-200 cells/mm3 and with HIV RNA above detection limit of the assay (AIII).
Treating PCP

Note—Patients who develop PCP despite TMP-SMX prophylaxis usually can be treated effectively with standard doses of TMP-SMX (BIII).

For Moderate to Severe PCP—Total Duration = 21 Days (AII):
Preferred Therapy:
  • TMP-SMX: (TMP 15–20 mg and SMX 75–100 mg)/kg/day IV given q6h or q8h (AI), may switch to PO after clinical improvement (AI).
Alternative Therapy:
  • Pentamidine 4 mg/kg IV once daily infused over at least 60 minutes (AI); may reduce the dose to 3 mg/kg IV once daily because of toxicities (BI) or
  • Primaquineb 30 mg (base) PO once daily + (Clindamycin [IV 600 q6h or 900 mg q8h] or [PO 450 mg q6h or 600 mg q8h]) (AI).
**Adjunctive corticosteroids are indicated in moderate to severe cases (see indications and dosage recommendations below)

For Mild to Moderate PCP—Total Duration = 21 days (AII):
Preferred Therapy:
  • TMP-SMX: (TMP 15–20 mg/kg/day and SMX 75–100 mg/kg/day), given PO in 3 divided doses (AI) or
  • TMP-SMX DS - 2 tablets TID (AI).
Alternative Therapy:
  • Dapsoneb 100 mg PO daily + TMP 15 mg/kg/day PO (3 divided doses) (BI) or
  • Primaquineb 30 mg (base) PO daily + Clindamycin PO (450 mg q6h or 600 mg q8h) (BI) or
  • Atovaquone 750 mg PO BID with food (BI)
Adjunctive Corticosteroids:
For Moderate to Severe PCP Based on the Following Criteria (AI):
  • PaO2 <70 mmHg at room air or
  • Alveolar-arterial O2 gradient ≥35 mm Hg
Dosing Schedule:
Prednisone doses (beginning as early as possible and within 72 hours of PCP therapy) (AI):

Days 1–5 40 mg PO BID
Days 6–10 40 mg PO daily
Days 11–21 20 mg PO daily

IV methylprednisolone can be given as 75% of prednisone dose
Preventing Subsequent Episode of PCP (Secondary Prophylaxis)

Indications for Initiating Secondary Prophylaxis:
  • Prior PCP
Preferred Therapy:
  • TMP-SMX, 1 DS PO dailya (AI) or
  • TMP-SMX, 1 SS PO dailya (AI).
Alternative Therapy:
  • TMP-SMX 1 DS PO three times weekly (BI) or
  • Dapsoneb,c 100 mg PO daily or 50 mg PO BID (BI) or
  • Dapsoneb 50 mg PO daily + (pyrimethamine 50 mg + leucovorin 25 mg) PO weekly (BI) or
  • (Dapsoneb 200 mg + pyrimethamine 75 mg + leucovorin 25 mg) PO weekly (BI) or
  • Aerosolized pentamidinec 300 mg via Respigard II™ nebulizer every month (BI) or
  • Atovaquone 1500 mg PO daily with food (BI) or
  • (Atovaquone 1500 mg + pyrimethamine 25 mg + leucovorin 10 mg) PO daily with food (CIII)
Indications for Discontinuing Secondary Prophylaxis:
  • CD4 count increased from <200 cells/mm3 to >200 cells/mm3 for >3 months as a result of ART (BII) or
  • Can consider if CD4 count 100-200 cells/µL and HIV RNA remain below limits of detection for at least 3-6 months (BII)
  • For patients in whom PCP occurs at a CD4 count >200 cells/mm3 while not on ART, discontinuation of prophylaxis can be considered once HIV plasma RNA levels are suppressed to below limits of detection for at least 3 to 6 months, although there are no data to support recommendations in this setting (CIII).
Note: If an episode of PCP occurs at a CD4 count >200 cells/mm3 while on ART, it would be prudent to then continue PCP prophylaxis for life, regardless of how high the CD4 cell count rises as a consequence of ART (BIII).

Indications for Restarting Secondary Prophylaxis:
  • CD4 count falls to <200 cells/mm3 (AIII) or
Other Considerations/Comments:
  • For patients with non-life-threatening adverse reactions to TMP-SMX, the drug should be continued if clinically feasible.
  • If TMP-SMX is discontinued because of a mild adverse reaction, re-institution should be considered after the reaction has resolved (AII). The dose can be increased gradually (desensitization) (BI) or given at a reduced dose or frequency (CIII).
  • Therapy should be permanently discontinued, with no rechallenge, in patients with possible or definite Stevens-Johnson Syndrome or toxic epidermal necrolysis (AIII).
a TMP-SMX DS once daily also confers protection against toxoplasmosis and many respiratory bacterial infections; lower dose also likely confers protection.
b Whenever possible, patients should be tested for G6PD deficiency before administration of dapsone or primaquine. Alternative agent should be used if the patient is found to have G6PD deficiency.
c Aerosolized pentamidine or dapsone (without pyrimethamine) should not be used for PCP prophylaxis in patients who are seropositive for Toxoplasma gondii.

Key to Acronyms: BID = twice daily; DS = double strength; IV = intravenously; PCP = Pneumocystis pneumonia; PO = orally; q “n” h = every “n” hour; SS = single strength; TID = three times daily; TMP = trimethoprim; TMP-SMX = trimethoprim-sulfamethoxazole  

Download Guidelines